Quantification and pharmacokinetics of Taiwanin E methyl ether in rats by liquid chromatography–tandem mass spectrometry

This study firstly describes the development of an accurate and sensitive high‐performance liquid chromatography–tandem mass spectrometry (LC‐MS/MS) assay for the quantification of Taiwanin E methyl ether (TEME) in rat plasma. The assay involved a simple liquid–liquid extraction step with ethyl acetate and a gradient elution using a mobile phase consisting of water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid. Chromatographic separation was successfully achieved on an Agilent Zorbax‐C₁₈ column (2.1 × 50 mm, 3.5 µm) with a flow rate of 0.40 mL/min. The multiple reaction monitoring was based on the transitions of m/z = 379.1 → 320.1 for TEME and 386.1 → 122.0 for buspirone (internal standard). The assay was validated to demonstrate the specificity, linearity, recovery, accuracy, precision and stability. The lower limit of quantification was 0.50 ng/mL in 50 μL of rat plasma. The developed and validated method was successfully applied to the quantification and pharmacokinetic study of TEME in rats after intravenous and oral administration of 1.45 mg/kg TEME. The oral absolute bioavailability of TEME was estimated to be 5.85 ± 1.41% with an elimination half‐life value of 2.61 ± 0.55 h, suggesting its poor absorption and/or strong metabolism in vivo. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of cefdinir levels in rat plasma and urine by high‐performance liquid chromatography–tandem mass spectrometry: application to pharmacokinetics after oral and intravenous administration of cefdinir

A selective and sensitive liquid chromatography tandem mass spectrometry method (LC‐MS/MS) was developed and validated for the determination of cefdinir in rat plasma and urine. Following a simple protein precipitation using methanol, chromatographic separation was achieved with a run time of 10 min using a Synergi 4 µ polar‐RP 80A column (150 × 2.0 mm, 4 µm) with a mobile phase consisting of 0.1% formic acid in water and methanol (65:35, v/v) at a flow rate of 0.2 mL/min. The protonated precursor and product ion transitions for cefdinir (m/z 396.1 → 227.2) and cefadroxil, an internal standard (m/z 364.2 → 208.0) were monitored in the multiple reaction monitoring in positive ion mode. The calibration curves for plasma and urine were linear over the concentration range 10–10,000 ng/mL. The lower limit of quantification was 10 ng/mL. All accuracy values were between 95.1 and 113.0% and the intra‐ and inter‐day precisions were <13.0% relative standard deviation. The stability under various conditions in rat plasma and urine was also found to be acceptable at three concentrations. The developed method was applied successfully to the pharmacokinetic study of cefdinir after oral and intravenous administration. Copyright © 2013 John Wiley & Sons, Ltd.     

Validated LC‐MS method for simultaneous quantitation of catalpol and harpagide in rat plasma: application to a comparative pharmacokinetic study in normal and diabetic rats after oral administration of Zeng‐Ye‐Decoction

A simple and efficient liquid chromatography‐mass spectrometry (LC‐MS) method was developed and validated for simultaneous quantitation of catalpol and harpagide in normal and diabetic rat plasma. Protein precipitation extraction with acetonitrile was carried out using salidroside as the internal standard (IS). The LC separation was performed on an Elite C₁₈ column (150 × 4.6 mm, 5 µm) with the mobile phase consisting of acetonitrile and water within a runtime of 12.0 min. The analytes were detected without endogenous interference in the selected ion monitoring mode with positive electrospray ionization. Calibration curves offered satisfactory linearity (r > 0.99) at linear range of 0.05–50.0 µg/mL for catalpol and 0.025–5.0 µg/mL for harpagide with the lower limits of quantitation of 0.05 and 0.025 µg/mL, respectively. Intra‐ and inter‐day precisions (RSD) were <9.4%, and accuracy (RE) was in the ?6.6 to 4.9% range. The extraction efficiencies of catalpol, harpagide and IS were all >76.5% and the matrix effects of the analytes ranged from 86.5 to 106.0%. The method was successfully applied to the pharmacokinetic study of catalpol and harpagide after oral administration of Zeng‐Ye‐Decoction to normal and diabetic rats, respectively. Copyright © 2013 John Wiley & Sons, Ltd.     

Development of an LC/MS/MS method in order to determine arctigenin in rat plasma: its application to a pharmacokinetic study

In this study, a simple and sensitive LC/MS/MS method was developed and validated for the determination of arctigenin in rat plasma. The MS detection was performed using multiple reaction monitoring at the transitions of m/z 373.2 → 137.3 for arctigenin and m/z 187.1 → 131.0 for psoralen (internal standard) with a Turbo IonSpray electrospray in positive mode. The calibration curves fitted a good linear relationship over the concentration range of 0.2–500 ng/mL. It was found that arctigenin is not stable enough at both room temperature and ?80 °C unless mixed with methanol before storage. The validated LC/MS/MS method was successfully applied for the pharmacokinetic study of arctigenin in rats. After intravenous injection of 0.3 mg/kg arctigenin injection to rats, the maximum concentration, half‐life and area under the concentration–time curve were 323 ± 65.2 ng/mL, 0.830 ± 0.166 and 81.0 ± 22.1 h ng/mL, respectively. Copyright © 2013 John Wiley & Sons, Ltd.     

Determination of antazoline hydrochloride in rat plasma and excreta by reversed‐phase ion‐pair chromatography and its application to pharmacokinetics

A reversed‐phase ion pair chromatography method with liquid–liquid extraction analytical method was developed and validated for the determination of antazoline hydrochloride in plasma and excreta of rat. The aim of our study was to characterize the preclinical pharmacokinetics and excretion profiles of antazoline hydrochloride in rats after intravenous injection at the dose of 10 mg/kg. Plasma and excreta samples were extracted with ethyl acetate, and phenacetin was used as the internal standard. The result showed that the method is suitable for the quantification of antazoline hydrochloride in plasma and excreta samples. Analysis of accuracy (90.89–112.33%), imprecision (<7.1%) and recovery (>82.5%) showed adequate values. After a single intravenous administration at 10 mg/kg to rats, plasma concentration profile showed a relative fast elimination proceeding with a terminal elimination half‐life of 3.53 h. Approximately 61.8 and 14.2% of the administered dose were recovered in urine and bile after 72 and 24 h post‐dosing respectively; 5.9% of the administered dose was recovered in feces after 72 h post‐dosing. The above results show that the major elimination route is urinary excretion. Copyright © 2013 John Wiley & Sons, Ltd.     

Identification and quantification of the antipsychotics risperidone,aripiprazole, pipamperone and their major metabolites in plasma using ultra‐high performance liquid chromatography–mass spectrometry

The antipsychotics risperidone, aripiprazole and pipamperone are frequently prescribed for the treatment in children with autism. The aim of this study was to validate an ultra‐high performance liquid chromatography–mass spectrometry method for the quantification of these antipsychotics in plasma. An ultra‐high performance liquid chromatography–mass spectrometry assay was developed for the determination of the drugs and metabolites. Gradient elution was performed on a reversed‐phase column with a mobile phase consisting of ammonium acetate, formic acid in methanol or in Milli‐Q ultrapure water at a flow rate of 0.5 mL/min. The method was validated according to the US Food and Drug Administration guidelines. The analytes were found to be stable enough after reconstitution and injection of only 5 μL improved the accuracy and precision in combination with the internal standard. Calibration curves of all five analytes were linear. All analytes were stable for at least 72 h in the autosampler and the high quality control of 9‐OH‐risperidone was stable for 48 h. The method allows quantification of all analytes. The advantage of this method is the combination of a minimal injection volume, a short run‐time, an easy sample preparation method and the ability to quantify all analytes in one run. Copyright © 2015 John Wiley & Sons, Ltd.     

A rapid and sensitive UPLC‐MS/MS method for quantification of two caffeoylquinic acids and four main active components in rat plasma after an intravenous administration of Qingkailing injection and its application to a pharmacokinetic study

Qingkailing (QKL) injection, a modified modern Chinese medicine preparation, is widely used in the clinic for its significant antipyretic and anti‐inflammatory effects, but its serious adverse drug reactions have attracted more and more attention. Series of caffeoylquinic acids in QKL are widely suspected to be the allergens responsible for these adverse drug reactions. Therefore, pharmacokinetic studies of the caffeoylquinic acids are needed. In this paper, a simple, rapid and sensitive ultra‐performance liquid chromatography–tandem mass spectrometry method was developed for the simultaneous determination of chlorogenic acid, neochlorogenic acid, baicalin, geniposide, cholic acid and hyodeoxycholic acid in rat plasma. Chromatographic separation was achieved on a BEH C₁₈ column by a gradient elution at a flow rate of 0.40 mL/min in only 6.0 min. All analytes were monitored by multiple reaction monitoring mode with negative electrospray ionization. The calibration curves of these analytes were all linear (r > 0.9978) over wide concentration ranges. The intra‐ and inter‐ day precisions (relative standard deviations) were within 14.3% and accuracy (relative error) ranged from ?6.8 to 4.8%. The mean recoveries ranged from 74.5 to 105.6%. This validated method was successfully applied to the pharmacokinetic study of the six analytes in rats following an intravenous administration of QKL injection. Copyright © 2013 John Wiley & Sons, Ltd.     

Determination of ecliptasaponin A in rat plasma and tissues by liquid chromatography‐tandem mass spectrometry

A sensitive, rapid and specific high‐performance liquid chromatography tandem mass spectrometry method (HPLC‐MS/MS) was developed to determine ecliptasaponin A in rat plasma and tissues after oral administration. Ginsenoside Rg1 was used as the internal standard (IS). The plasma and tissues samples were prepared by liquid‐liquid extraction with ethyl acetate and separated on an Eclipse Plus C₁₈ column (2.1 mm × 150 mm, 5 µm) at a flow rate of 0.4 mL/min using acetonitrile and water (containing 0.05% acetic acid) as the mobile phase. The tandem mass detection was carried out with eletrospray ionization in negative mode. Quantification was performed by using multiple reaction monitoring (MRM), which monitored the fragmentation of m/z 633.4→587.2 for ecliptasaponin A and m/z 859.4→637.4 for the IS. The calibration curves obtained were linear in different matrices, and the lower limit of quantification (LLOQ) achieved was 0.5 ng/mL both for rat plasma and tissues. The intra‐ and inter‐day precisions were below 15%. This method was successfully applied to pharmacokinetic study of ecliptasaponin A in rat plasma and tissues after oral administration. Copyright © 2015 John Wiley & Sons, Ltd.     

A sensitive LC–MS/MS‐based bioanalytical method for quantification of salviaflaside and rosmarinic acid in rat plasma and its application in a pharmacokinetic study

A selective and sensitive liquid chromatography tandem mass spectrometry method was developed for the simultaneous determination of salviaflaside and rosmarinic acid in rat plasma. Sample preparation was carried out through liquid–liquid extraction with ethyl acetate using curculigoside as internal standard (IS). The analytes were determined by selected reaction monitoring operated in the positive ESI mode. Chromatographic separation was performed on an Agilent Eclipse Plus C₁₈ column (100 × 4.6 mm, 1.8 μm) with a mobile phase consisting of methanol–water–formic acid (50:50:0.1, v/v/v) at a flow rate of 0.3 mL/min. The run time was 1.9 min per sample and the injection volume was 5 μL. The method had an LLOQ of 1.6 ng/mL for salviaflaside and 0.94 ng/mL for rosmarinic acid in plasma. The linear calibration curves were fitted over the range of 1.6–320 ng/mL for salviaflaside and 0.94–188 ng/mL for rosmarinic acid in plasma with correlation coefficients (r²) >0.99. Intra‐ and inter‐day precisions (relative standard deviation) were < 13.5%, and accuracies (relative error) were between −8.6% and 14.5% for all quality control samples. The method was validated and applied to the pharmacokinetics of salviaflaside and rosmarinic acid in plasma after oral administration of Prunella vulgaris extract to rats.     

Determination and validation of chikusetsusaponin IVa in rat plasma by UPLC‐MS/MS and its application to pharmacokinetic study

A novel, sensitive and rapid ultra‐performance liquid chromatography–tandem mass spectrometric method for the quantification of chikusetsusaponin IVa (CHS‐IVa) in rat plasma was established and validated. Plasma samples were pre‐treated by precipitation of protein with acetonitrile and chromatographed on a Waters Symmetry C₁₈ analytical column (4.6 × 50 mm, i.d., 3.5 μm) using a mobile phase consisting of methanol and water containing 0.05% formic acid (55:45, v/v) at a flow rate of 0.4 mL/min. The deprotonated molecular ions [M ? H]^– were employed in electrospray negative ionization mode and selected reaction monitoring transitions were performed for detection. The calibration curves exhibited good linearity (r > 0.99) over the range of 0.5–1000 ng/mL for CHS‐IVa. The recoveries of CHS‐IVa were >92.5% and exhibited no severe matrix effect. This method was successfully applied in the pharmacokinetic study of CHS‐IVa in rats. For oral administration, the plasma concentrations of CHS‐IVa increased to a peak value at 0.35 ± 0.14 h, followed by a gradual decrease to the lower limit of quantitation in 24 h. For intravenous administration, the plasma concentrations of CHS‐IVa decreased quickly (t_1/2, 1.59 ± 0.25 h). The absolute bioavailability of CHS‐IVa in rats was 8.63%. Copyright © 2016 John Wiley & Sons, Ltd.